THE OCCURRENCE AND CLINICAL RELEVANCE OF FIBRIN FRAGMENTS IN BLOOD

The measurement of fibrin degradation products (FDP) in blood has been fashionable for some time and the availability of various methodologies has influenced the interpretation of the FDP assay. The term “FDP” has been subject to a deal of misinterpretation, ranging from a misconception about the source of the FDP fraction in blood to fundamental communication problems between those knowledgeable in fibrin-fibrinogen biochemistry and those who actually measure FDP in blood. The term “FDP” was often used to mean fibrinogen and fibrin degradation products; whereas this can indeed be true, it is now generally accepted that the FDP fraction mainly results from the interaction of plasmin with fibrin rather than fibrinogen.’ It is well to keep in mind that the interaction of fibrin with other enzymes is also a possible source of the FDP fraction.2 Thus in most cases of blood FDP the investigator is measuring the plasmin-mediated fragments derived from fibrin as it forms in the soluble state or is deposited, mostly in the microvasculature. A communication problem has been highlighted by the supposed measurement of fragment E rather than the whole FDP fraction, using tests based on antisera specific for the E domain of fibrinogen or of fibrin.g Staff in clinical laboratories may be under the impression that they can measure the E fragment, whereas in reality the early FDP fragments, such as X and Y, are the major source of the E antigen reacting in the immunologic assay. Thus “E antigen assays” are no more than modifications of existing FDP assays with an altered sensitivity and no real change in specificity. Since radioimmunoassays (RIA) are already adequately sensitive for the measurement of FDP in an undiluted plasma sample, any increase in sensitivity of these assays is disadvantageous *; it can be concluded that the “E antigen assay” in human serum is little more than a promotional modification that capitalizes on the erroneous impression that free fragment E is measured and that this may be clinically relevant. Despite these problems about the source and meaning of the FDP fraction in blood, highlighted by the examples given above, a note of optimism was sounded in 1972, when it was predicted that the cross-linked (XL) FDP fraction, notably D dimer,6 might clarify our understanding of clinical fibrinolysis and serve as a useful diagnostic tool of the prethrombotic state. Ten years on the implementation of this hopeful prediction remains unfulfilled. However, during this time our understanding of the digestion of fibrin by plasmin has increased via the characterization of plasmin-mediated XL-FDP in vitro,‘* and the presence of a whole family of XL derivatives has been established beyond doubt in various body fluids.9 Limited characterization of XL-FDP found in vivo has been achieved, and an effort is made here to collate some of the more recent reports in this area. Efforts are also made to relate these FDP fractions to the type of fibrin from which it came and to access the

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